Wnt proteins synergize to activate β-catenin signaling.

Published

Journal Article

Wnt ligands are involved in diverse signaling pathways that are active during development, maintenance of tissue homeostasis and in various disease states. While signaling regulated by individual Wnts has been extensively studied, Wnts are rarely expressed alone, and the consequences of Wnt gene co-expression are not well understood. Here, we studied the effect of co-expression of Wnts on the β-catenin signaling pathway. While some Wnts are deemed 'non-canonical' due to their limited ability to activate β-catenin when expressed alone, unexpectedly, we find that multiple Wnt combinations can synergistically activate β-catenin signaling in multiple cell types. WNT1- and WNT7B-mediated synergistic Wnt signaling requires FZD5, FZD8 and LRP6, as well as the WNT7B co-receptors GPR124 (also known as ADGRA2) and RECK. Unexpectedly, this synergistic signaling occurs downstream of β-catenin stabilization, and is correlated with increased lysine acetylation of β-catenin. Wnt synergy provides a general mechanism to confer increased combinatorial control over this important regulatory pathway.

Full Text

Duke Authors

Cited Authors

  • Alok, A; Lei, Z; Jagannathan, NS; Kaur, S; Harmston, N; Rozen, SG; Tucker-Kellogg, L; Virshup, DM

Published Date

  • May 1, 2017

Published In

Volume / Issue

  • 130 / 9

Start / End Page

  • 1532 - 1544

PubMed ID

  • 28289266

Pubmed Central ID

  • 28289266

Electronic International Standard Serial Number (EISSN)

  • 1477-9137

Digital Object Identifier (DOI)

  • 10.1242/jcs.198093

Language

  • eng

Conference Location

  • England